Abrupt-mediated control of Ninjurins regulates Drosophila sessile hemocyte compartments

Macrophage-like cells called hemocytes are key effectors of Drosophila cellular innate immune function. Larval hemocytes exist either in circulation or localise to segmentallyrepeated sessile hemocyte compartments (SHCs). While numerous functions have been proposed for SHCs, the mechanisms directing hemocytes to them are unclear. Here, we have exploited the developmentally-regulated dispersal of SHCs that occurs at pupariation to identify the Abrupt (Ab) transcription factor (TF) and Ninjurin cell adhesion molecules as regulators of hemocyte recruitment to SHCs. We show that larval hemocytes express Ninjurins which are required for targeting hemocytes to SHCs. However, at pupariation, ecdysteroid signaling stimulates Ab expression, which collaborates with TFs including Blimp-1 and Hr3 to repress Ninjurins and disperse hemocytes. We observe that experimental manipulations that antagonise Ninjurin function in larval hemocytes cause premature SHC dispersal, while stabilization of Ninjurins in hemocytes blocks developmentally-regulated SHC remodeling and increases sensitivity to immune challenges. Cumulatively, our data indicate that control of Ninjurin activity provides a common target through which diverse developmental, environmental, and immune stimuli can be integrated to control hemocyte dispersal and immune function.